Reduced accumbens dopamine in Sprague–Dawley rats prone to overeating a fat-rich diet

Abstract

Obese humans and animals exhibit reduced functioning of the dopamine (DA) system in the nucleus accumbens (NAc). The question addressed here is whether this change in NAc DA can be detected in Sprague-Dawley rats that are prone to obesity on a fat-rich diet but still at normal body weight. Rats were subgrouped as “obesity-prone” (OP) or “obesity-resistant” (OR), based on their weight gain during 5 days of access to a high-fat diet, and were then shifted to a lower-fat chow diet before microdialysis testing was performed. The OP rats compared to OR rats exhibited markedly reduced basal levels of DA in the NAc. After a high-fat challenge meal, both OP and OR rats showed a significant increase in extracellular DA and its metabolites; however, the NAc DA of the OP rats still remained at reduced levels. Also, the increase in DA and metabolite levels observed in OR rats after systemic administration of a fat emulsion was not evident in the OP rats, which instead showed no change in DA and a decrease in its metabolites. These results demonstrate, first, that fat can stimulate accumbal DA release and, second, that outbred rats prone to overeating and becoming obese on a palatable, fat-rich diet exhibit reduced signaling in the mesolimbic DA system while still at normal weight, suggesting that it may be causally related to their excess consummatory behavior.

Elevated Dopamine D2/3 Receptor Availability in Obese Individuals: A PET Imaging Study with [11C](+)PHNO

“…Although debate still exists whether this can be Seeman, 2012;Skinbjerg et al, 2012), in theory, only agonist tracers like [ 11 C](+)PHNO would prefer these sites as D 2/3 R antagonist tracers typically bind with equal preference to both high-and low-affinity forms of the D 2/3 R. Therefore, it is possible that these differential binding characteristics could also help explain our VST findings such that the regulation of 'active' highaffinity forms vs 'inactive' low-affinity forms of the D 2/3 R may be altered in obesity. Our finding in the VST is also consistent with the previous [ 11 C](+)PHNO work in non-OB individuals (Caravaggio et al, 2013) and preclinical research that posits the nucleus accumbens, a central component of the VST, plays a key role in the formation/development of the OB phenotype (Davis et al, 2008;Geiger et al, 2009;Hryhorczuk et al, 2016;Rada et al, 2010;Valenza et al, 2015). This regional specificity, along with tracer properties, may help explain why differences were not found in the dorsal striatum.…”

“…[ 11 C](+)PHNO has been shown to be substantially more sensitive to endogenous dopamine competition (ie, increased tracer displacement resulting in lower BP ND ) compared with the antagonist tracers used in prior studies (Cropley et al, 2008;Gallezot et al, 2014a;Ginovart et al, 2006;Moerlein et al, 1997;Shotbolt et al, 2012;Willeit et al, 2008); thus, our receptor availability findings could also be due to OB individuals exhibiting lower levels of tonic dopamine. In fact, this concept is consistent with prior reports that have shown dietinduced OB and OB-prone rats exhibited lower levels of tonic dopamine or less dopaminergic-mediated behaviors (ie, conditioned place preference or amphetamine-induced locomotor activity) compared with standard chow fed or OB-resistant controls (Geiger et al, 2009;Hryhorczuk et al, 2016;Rada et al, 2010).…”

Central lipid detection and the regulation of feeding behavior

“…In agreement with this hypothesis, when the orosensory reward of fat is bypassed with i.p. injection of triglycerides (TG) the increase in TG levels rats leads to an increase in both DA and and DA metabolites in the Nacc, similar what is observed after the fat consumption (Rada et al, 2010). These result suggest that, as glucose, TG could act as a signaling molecule in dopamine system and could be part of the reinforcing effects of palatable food.…”

Influence of dopamine and its receptors in the genesis of obesity: systematic review

“…Não é claro se o hipofuncionamento do sistema dopaminérgico se manifesta antes do desenvolvimento da obesidade ("síndrome da deficiência de recompensa"), ou se a obesidade é causa das alterações na neurotransmissão Em outro estudo experimental, foram demonstrados baixos níveis de dopamina no NAcc de ratos propensos à obesidade, o que os motiva a buscar mais alimentos, na tentativa de regular os níveis deste neurotransmissor 23 . Similarmente, outros autores observaram redução dos níveis de dopamina no NAcc, córtex pré--frontal medial e estriado dorsal de ratos propensos à obesidade (OP) 24 e, em outro trabalho, notaram redução na exocitose de dopamina em neurônios pré-sinápticos no NAcc de animais obesos, quando comparados com o grupo controle não-obeso 25 .…”

“…Nos EUA, as taxas de sobrepeso e obesidade estão em constante aumento, com cerca de 35% da população adulta de ambos os sexos obesa, enquanto a taxa em adolescentes e crianças obesos chega até 15 a 30% 36 . Isso pôde ser evidenciado no fato de a maioria dos estudos (12 dos 17) ter sido conduzida nos EUA [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] .…”